Thomas Lee Ortel, MD, PhD

Professor of Medicine
Chief, Division of Hematology in the Department of Medicine
Professor of Pathology
Member of the Duke Cancer Institute
Campus mail 0563 Stead Bldg, Durham, NC 27710
Phone (919) 684-5350
Email address ortel001@mc.duke.edu

My research program investigates the molecular mechanisms whereby various congenital and acquired abnormalities result in ‘dysfunctional’ hemostasis (i.e., hemorrhage or thrombosis) to better understand the molecular mechanisms and interactions that are necessary for normal hemostasis. We are particularly interested in the mechanisms whereby antibodies and other inhibitors can interfere with normal hemostatic mechanisms. Several projects extensively overlap and focus on the assembly and function of procoagulant (e.g., factor X-ase and prothrombinase) and anticoagulant (e.g., activated protein C complex) phospholipid membrane-dependent complexes.

We utilize a variety of approaches in these studies. Monoclonal antibodies, single-chain variable domain fragments, polyclonal antibodies prepared from patients with factor VIII inhibitors, and site-specific mutagenesis have all been used to characterize structure-function relationships in coagulation factor VIII. Our laboratory has also extensively characterized anti-factor V antibodies, investigating autoantibodies as well as xenogenic antibodies developing after exposure to topical bovine thrombin preparations which contain trace amounts of contaminating bovine factor V. We have also characterized how antiphospholipid antibodies interfere with the activated protein C complex, a lipid-dependent natural anticoagulant complex that proteolytically inactivates factor Va and factor VIIIa.

Our current studies are focusing on two antibody-mediated thrombotic syndromes, heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. First, we are initiating a large clinical trial investigating the incidence of clinically-significant heparin-induced thrombocytopenia in patients who develop anti-heparin/platelet factor 4 antibodies following cardiac bypass procedures. While these antibodies are commonly seen following cardiac bypass, the true incidence of thromboembolic complications related to these prothrombotic antibodies remains unknown. We are also collaborating with investigators in the Center for Human Genetics on a large, multi-center study exploring the genetics of familial antiphospholipid antibody syndrome. In addition, we have used a genomic strategy to investigate patients with antiphospholipid antibody syndrome and have identified a gene expression profile that appears to be unique to patients with this syndrome in contrast to patients with venous thromboembolism who do not have these autoantibodies.

We also participate in a variety of collaborative research efforts, both with individual investigators as well as participating in multi-center clinical research studies. For example, we are one of seventeen centers participating in the NIH-supported Transfusion Medicine/Hemostasis Network, and we are currently conducting a trial through this network to define the optimal dose of platelets for patients needing platelet transfusions for hypoproliferative thrombocytopenia. We are also part of a multi-center registry of patients with thrombotic thrombocytopenic purpura, and we are one of eight centers in the Hemostasis and Thrombosis Center pilot program sponsored by the Centers for Disease Control and Prevention. Participation in these registries and networks provides us with access to the patient populations that we study in the research laboratory.

In Their Words

Education and Training

  • Fellow in Hematology-Oncology, Medicineq, Duke University, 1988 - 1991
  • Medical Resident, Medicine, Duke University, 1985 - 1988
  • M.D., Indiana University at Indianapolis, 1985
  • Ph.D., Indiana University at Bloomington, 1983

Publications

Macik, BG, and Ortel, TL. "Clinical and laboratory evaluation of the hypercoagulable states." Clin Chest Med 16, no. 2 (June 1995): 375-387. (Review)

PMID
7656547
Scholars@Duke

Keller, FG, Ortel, TL, Quinn-Allen, MA, and Kane, WH. "Thrombin-catalyzed activation of recombinant human factor V." Biochemistry 34, no. 12 (March 28, 1995): 4118-4124.

PMID
7696276
Scholars@Duke

Joyner, KA, and Ortel, TL. "A Sensitive DRVVT Reagent System for the Detection of Lupus Anticoagulants." Clinical and Applied Thrombosis/Hemostasis 1, no. 1 (January 1995): 73-75.

Full Text

Greenberg, CS, Hursting, MJ, Macik, BG, Ortel, TL, Kane, WH, and Moore, BM. "Evaluation of preanalytical variables associated with measurement of prothrombin fragment 1.2." Clin Chem 40, no. 10 (October 1994): 1962-1969.

PMID
7923780
Scholars@Duke

Charles, LA, McGlasson, DL, Hawksworth, BA, Ashcraft, JH, and Ortel, TL. "Evaluation of a modified procedure for Staclot LA for the confirmation of lupus anticoagulants." Blood Coagul Fibrinolysis 5, no. 4 (August 1994): 601-604.

PMID
7841317
Scholars@Duke

Provenzale, JM, Heinz, ER, Ortel, TL, Macik, BG, Charles, LA, and Alberts, MJ. "Antiphospholipid antibodies in patients without systemic lupus erythematosus: neuroradiologic findings." Radiology 192, no. 2 (August 1994): 531-537.

PMID
8029427
Full Text

Ortel, TL, Quinn-Allen, MA, Keller, FG, Peterson, JA, Larocca, D, and Kane, WH. "Localization of functionally important epitopes within the second C-type domain of coagulation factor V using recombinant chimeras." J Biol Chem 269, no. 22 (June 3, 1994): 15898-15905.

PMID
7515064
Scholars@Duke

Ortel, TL, Charles, LA, Keller, FG, Marcom, PK, Oldham, HN, Kane, WH, and Macik, BG. "Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum and laboratory diagnosis." Am J Hematol 45, no. 2 (February 1994): 128-135. (Review)

PMID
8141118
Scholars@Duke

Wiedmer, T, Hall, SE, Ortel, TL, Kane, WH, Rosse, WF, and Sims, PJ. "Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria." Blood 82, no. 4 (August 15, 1993): 1192-1196.

PMID
7688991
Scholars@Duke

Ortel, TL, Quinn-Allen, MA, Charles, LA, Devore-Carter, D, and Kane, WH. "Characterization of an acquired inhibitor to coagulation factor V. Antibody binding to the second C-type domain of factor V inhibits the binding of factor V to phosphatidylserine and neutralizes procoagulant activity." J Clin Invest 90, no. 6 (December 1992): 2340-2347.

PMID
1281831
Full Text

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